Creutzfeldt-Jakob disease (CJD)is a rapidly progressive, universally fatal, and transmissible neurodegenerative disease that imposes a terrible burden on patients and their families. The recent discovery that quinacrine may be a potential therapy for CJD could have enormous implications for patients. Unfortunately, patients are usually diagnosed in advanced stages of the disease - a time when available treatments may be ineffective. This delayed diagnosis is in part because current clinical criteria for sporadic CJD (sCJD) are based on a constellation of symptoms that often occur only late in a patient's course. Recently, neuroimaging has shown potential to improve the diagnosis of sCJD. Additionally, an elevated level of the protein 14-3-3 in the cerebrospinal fluid (CSF) has been touted as a sensitive and specific biomarker for sCJD and has recently been added to the diagnostic criteria for sCJD. Yet, no systematic study has been undertaken to identify the sensitivity and specificity of these two types of biomarkers in pathologically proven sCJD versus non-prion rapidly progressive dementias. The research goals of this proposal focus on identifying better ways for early diagnosis of CJD through a systematic analysis of clinical and imaging findings. The specific aims of this research will be as follows: 1 . To determine the sensitivity and specificity of diffusion-weighted imaging (DWI) sequence abnormalities in sporadic CJD, and 2. To determine the sensitivity and specificity of the CSF 14-3-3 protein as a marker for sporadic CJD. This research should provide new information on the early features of sCJD and thus facilitate diagnosis. In addition, this proposal will combine didactic teaching, mentoring, and clinical research experience to build upon Dr. Geschwind's training in behavioral neurology and neuroscience, thereby helping him to design and implement future clinical treatment studies for human prion disease and other dementias.